Remodeling of colon plasma cell repertoire within ulcerative colitis patients

• DOI: 10.1084/jem.20220538
• Publication Date: 2023-02-08T14:38:45Z
• Authors: Johannes F. Scheid; Basak Eraslan; Andrew Hudak; Eric M. Brown; Dallis Sergio; Toni M. Delorey; Devan Phillips; Ariel Lefkovith; Alison T. Jess; Lennard W. Duck; Charles O. Elson; Hera Vlamakis; Damian R. Plichta; Jacques Deguine; Ashwin N. Anantha...; Daniel B. Graham; Aviv Regev; Ramnik J. Xavier
• Keywords: Isotype; Pathogenesis

Plasma cells (PCs) constitute a significant fraction of colonic mucosal and contribute to inflammatory infiltrates in ulcerative colitis (UC). While gut PCs secrete bacteria-targeting IgA antibodies, their role UC pathogenesis is unknown. We performed single-cell V(D)J- RNA-seq on sorted B from the colon healthy individuals patients with UC. A large cell clones shared between different regions, but inflammation broadly disrupts this landscape, causing transcriptomic changes characterized by an increase unfolded protein response (UPR) antigen presentation genes, clonal expansion, isotype skewing IgA1 IgA2 IgG1. also directly expressed assessed specificity 152 mAbs expanded PC clones. These show low polyreactivity autoreactivity instead target both bacterial antigens specific strains. Altogether, our results characterize microbiome-specific how its disruption might